Reducing the Burden of Biopsy: An Institutional Time Series Analysis

Purpose Acute rejection is an important complication following Heart Transplant (HT). The widespread use of peripheral blood markers can reduce the burden of biopsies. We assessed whether the rate of surveillance biopsies decreased after the introduction of gene expression profiling (GEP) in March 2013 and donor-derived cell-free DNA (cfDNA) in October 2018. Methods We analyzed the monthly biopsy time series after the introduction of GEP and cfDNA using an interrupted time series model for the 12 months prior to and after their introduction: GEP 02/12-02/13 v. 03/13-02/14 and for cfDNA 10/17-09/18 vs 10/18-09/19. For both models, an autoregressive regression model was applied to quantify the impact of the introduction of each intervention on the number of biopsies per patient-month. A Durban-Watson test was used to detect the presence of autocorrelation. Results Before the introduction of GEP, biopsies per patient-month were decreasing at a rate of 0.21 (95% CI = [-0.64, 0.23], p=0.35) per month. After the introduction of GEP there was a significant drop in per-patient monthly biopsies of 4.97 (95% CI = [-9.20, -0.74], p=0.021) (Fig1A) but rising at a rate of 0.34 per-patient-month after the initial drop. Similar to GEP, monthly biopsies per patient were already decreasing, at a monthly rate of 0.23 (95% CI = [-0.50, 0.04], p =0.095), before cfDNA was introduced. This introduction further steepened the downward trend in the per-patient-month biopsies at rate of 0.45 per month (Fig IB) despite a steady increase in the number of patients followed over the last 10 years (Fig 1D). Conclusion In a high-volume transplant center, the application of non-invasive testing with cfDNA and GEP has resulted in a considerable reduction in routine surveillance biopsies. Should these tests become widely accessible, GEP and cfDNA will likely provide a sustainable reduction in the biopsy burden across all programs.